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What Causes Schizophrenia? Genetics, Environment, Brain Chemistry, Brain Structure

Schizophrenia is a severe disease in which individuals are plagued with hallucinations, delusions, disorganized speech, as well as social dysfunction. Although an exact cause of the disease has not yet been discovered, researchers are aware that a number of factors may contribute to its development. Genetics, environment, brain structure, and brain chemistry can each be analyzed and broken down separately.

What Causes Schizophrenia?

There are a number of possible causes, but scientists have not been able to pinpoint an “exact” cause. There may be a number of contributing factors that play role in the development of this debilitating disorder. These contributing factors include: genetics, environment, brain chemistry, and brain structure.

Although scientists have associated specific things as being linked to schizophrenia, the causes remain a mystery. As research advances and we look at this disease from all angles, it is hoped that better treatment options and ultimately cure will be discovered.

1. Genetics

The fact is that if a person has one or more parents with schizophrenia, the likelihood of that individual developing schizophrenia increases drastically. When looking at severe disorders like schizophrenia, there is typically a strong genetic link.

  • 10% risk – If you have a first-degree relative with the disease.
  • 40% risk – If you have an identical twin with the disease.

Note: 60% of individuals that develop schizophrenia have no close relative with the illness.

This risk is lower than I would’ve suspected. I find that 10% risk is pretty low for having a first degree relative with the disease; my estimations would’ve been greater.

In regards to a genetic link to schizophrenia, it is nearly impossible to pin down an exact DNA sequence or gene for causing the disease. There are certain mutations and genes that we know are implicated. Scientists have developed hypotheses linking variations such as the:

  • NOTCH4
  • Histone H3
  • Zinc finger protein 804A
  • Neuregulin-1
  • OLIG2
  • COMT

Interestingly enough, there appears to be an overlap in the genetics of schizophrenia and bipolar disorder. I’m a huge advocate for genetic research because I believe that if we are going to get serious about curing this disease, we are going to need to permanently normalize / fix the genetics that are causing the symptoms.

Geneticists and researchers have questioned how schizophrenia developed and evolved in the first place. Some think that as language continued to evolve, certain genes also evolved and individuals actually started hearing voices. Obviously this is a maladaptive evolution in the eyes of many – including those coping with the disease.

2. Environment

As you should know, genetics are only part of the equation. If a person grows up in impoverished living conditions, the likelihood of mental health problems increases. In my mind, genetics are the trickiest and single most influential factor in diseases like schizophrenia. Although environment should still be analyzed, I feel as though if you have favorable genetics, the likelihood of developing this disease drops drastically.

Key environmental factors in schizophrenia

  • Parenting styles: No major link

Parenting styles have been analyzed in individuals with schizophrenia and they had no major influence on the development of this disease. Individuals with supportive parents generally cope better with their disease in comparison to those with neglectful or hostile parents. Similar findings have been made in an array of mental illnesses.

  • Urban environment: Increased risk (2x)

Growing up as a child in an urban environment has a significant link between increasing risk of schizophrenia by 2x. I’m wondering if this could be as a result of the increased stress associated with urban living in comparison to a more relaxed suburban or rural lifestyle. Maybe the stress activates or deactivates certain genes which would otherwise be dormant in adult life? I can only hypothesize.

  • Drug abuse: Possible increased risk

The drug that is most linked to increased risk of schizophrenia is cannabis (marijuana). There is evidence that use of marijuana contributes to earlier onset of the disease in those that are susceptible. Some argue that it there is actually a causal link between cannabis and schizophrenia.  For further reading, check out the article “Can Smoking Marijuana Cause Schizophrenia?”

Amphetamines and uppers like cocaine that release high amounts of dopamine into the brain can trigger a psychotic episode – but this is not the same thing as schizophrenia. This is called amphetamine induced psychosis – and is similar, but will eventually subside when the individual goes through a full blown amphetamine withdrawal. Perhaps the most interesting fact is that individuals with schizophrenia tend to use nicotine at significantly greater rates than the general population.  Many famous people with schizophrenia have a history of drug abuse prior to onset of the illness.

  • Social isolation: May increase risk

One factor that has been investigated regarding schizophrenia is that of “social isolation.” Researchers have wondered whether the isolation can be a direct contributing cause of the disease developing or whether it is merely a side effect of the disease. There’s a chicken vs. egg type argument here in regards to social isolation and schizophrenia.

  • Infection in womb: Increased risk

Mothers that are infected with viruses in the womb may put their offspring at greater risk for development of schizophrenia. Thus far scientists have discovered that in 30% of people with acute schizophrenia, a virus in the HERV-W retrovirus family was found.

  • Birth Season (Winter / Spring): Increased risk

There is an increased risk of 5% to 8% of developing schizophrenia as a baby born in a winter or spring season in the northern hemisphere. Some hypothesize this may be due to the likelihood of developing a virus in utero increases during these times of the year.

  • Big families: Slightly increased risk

In bigger families that have short gaps between births of their children (<2 years), there seems to be slightly greater risk of developing infections, which could lead to the development of schizophrenia.

  • Parasite: Possible increased risk

Certain studies have linked toxoplasmosis to schizophrenia. The interesting aspect of this is the fact that this parasite can go undetected in the nervous system for years. This parasite is primarily transferred to humans by cats. It can take many years for its effects to fully reach the brain.

  • Other factors: May increase risk

Several other factors including: immigration, viruses, malnutrition, hypoxia, racial discrimination, familial dysfunction, unemployment, poor housing conditions, and high amounts of stressors have all been hypothesized to be contributing factors.

Source: http://www.ncbi.nlm.nih.gov/pubmed/11329398

3. Brain chemistry

Differences in brain chemistry have been studied comparing those affected with schizophrenia to normal test subjects.  In most studies comparing those with schizophrenia to those without, fMRI and PET were used to compare brains.

Dopamine hypothesis – This suggests that psychosis is a result of dopaminergic neurons that are misfiring or dysfunctional. This is one of the most popular hypotheses in regards to brain chemistry causing schizophrenia. Generally it is widely accepted that an overload of dopamine is what causes positive symptoms such as: hallucinations and delusions.

Glutamate – Significantly low amounts of glutamate receptors (NMDA receptors) have been found in those diagnosed with schizophrenia. Due to the fact that an array of cognitive problems are linked to reductions in glutamate function, many have suggested these receptors may play an important role in the condition.

Lack of hemispheric synchrony – There is some evidence that points to the fact that the left and right hemispheres of the brain are unable to communicate with each other for the transfer of information and general functioning.

Neural circuitry – Is altered in those with schizophrenia – particularly in the mesolimbic pathway. Most think that excess activation of the D2 receptors lead to causing the positive symptoms of schizophrenia. PET scans have provided evidence supporting overactivation of the D2 receptors.

4. Brain structure

Altered brain connectivity – Individuals with this disease experience altered brain connectivity compared to normal subjects. The dysfunctional interaction between brain regions has been proposed to be a central feature of the illness.

Amygdala & limbic dysfunction – Deficits in amygdala reactivity and connectivity between amygdala and subgenual cingulated have also been implicated.

  • Frontal lobes
  • Temporal lobes
  • Hippocampus

Note: Most differences in people with schizophrenia tend to have significant functioning differences in the frontal lobes, hippocampus, as well as temporal lobe regions of the brain.

Brain volume – Those with schizophrenia tend to have significant reductions in overall brain volume. In fact, they tend to be even more severe than individuals affected with Alzehimer’s disease in the frontal cortex and temporal lobes.  Studies have been done comparing the brains of identical twins – one with schizophrenia and the other disease free. These comparisons have been able to show that smaller brain volume is a factor in those with schizophrenia. This smaller volume reduces ability to think, memorize, and concentrate on tasks.

Gray matter – Decreased gray matter has been found in several brain regions of those with this illness including: middle temporal gyrus, superior temporal gyrus, and anterior cingulated. Interestingly enough is the fact that there is a negative correlation between positive symptoms and gray matter volume.

White matter – Reduced amounts of white matter have been discovered in brain regions of those with schizophrenia compared to others. If you want to get more in depth, you can look up the specific regional differences and percentages.

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